The ultimate goal of these experiments is to understand the virus induced transformation of normal hemopoietic cells into leukemia cells. Although in vitro transformation of fibroblasts by RNA tumor viruses is routinely observed, remarkably few systems are available to study transformation of hemopoietic cells in vitro. The applicant has developed conditions which allow Friend virus induced erythroid transformation of bone marrow cells in vitro. This transformation results in the formation of erythroid bursts in the absence of added erythropoietin. The observed erythroid effect is large, rapid, and is produced by several different Friend virus preparations. This in vitro transformation system has, therefore, opened avenues of leukemia virus research which were not previously feasible. The applicant now proposes to further understand the viral transformation by examining several virologic aspects of this new in vitro transformation system. The parameters to be assessed include: the necessity for virus replication for erythroid burst formation, the genetic control of susceptibility to FV transformation in vitro and whether one virus (Spleen Focus Forming Virus, SFFV) or two viruses (SFFV and helper murine leukemia virus, MuLV) are needed to produce the erythroid transformation. For several murine RNA tumor viruses, erythroblastosis is a part of the diverse methodological conditions which they induce. We will test these preparations in vitro in an attempt to dissociate their erythroid actions in vitro from their other tumorigenic actions in vivo.